Essential Evidence-based Medicine, Second Edition (Essential ...

Koch’s postulates stated four basic steps to prove causation. First, the infectious
agent must be found in all cases of the illness. Second, when found it must
be able to be isolated from the diseased host and grown in a pure culture. Next,
the agent from the culture when introduced into a healthy host must cause the
illness. Finally, the infectious agent must again be recovered from the new host
and grown in a pure culture. This entire cascade must be met in order to prove
causation.
While this model may work well in the study of acute infectious diseases, most
modern illnesses are chronic and degenerative in nature. Illnesses such as diabetes,
heart disease, and cancer tend to be multifactorial in their etiology and
usually have multiple treatments that can alleviate the illness. For these diseases,
it is virtually impossible to pinpoint a single cause or the effect of a single treatment
from a single research study. Stronger studies of these diseases are more
likely to point to useful clinical information relating one particular cause with an
effect on the illness.
Applying contributory cause helps prove causation in these complex and multifactorial
diseases. The requirements for proof are less stringent than Koch’s
postulates. However, since the disease-related factors are multifactorial, it is
more difficult to prove that any one factor is decisive in either causing or curing
the disease. Contributory cause recognizes that there is a large gray zone in
which some of the many causes and treatments of a disease overlap.
First, the cause and effect must be seen together more often than would be
expected to occur by chance alone. This means that the cause and effect are associated
more often than would be expected by chance if the concurrence of those
two factors was a random event. Second, the cause must always be noted to precede
the effect. If there were situations for which the effect was noted before the
occurrence of the cause, that would negate this relationship in time. Finally and
ideally, it should be shown that changing the cause changes the effect. This last
factor is the most difficult to prove and requires an intervention study be performed.
Overall, contributory cause to prove the nature of a chronic and multifactorial
illness must minimally show association and temporality. However, to
strengthen the causation, the change of the effect by a changing cause must also
be shown. Table 3.1 compares Koch’s postulates and contributory cause.
Causation and the clinical question
The two main components of causation are also parts of the clinical question.
Since the clinical question is the first step in EBM, it is useful to put the clinical
question into the context of causation. The intervention is the cause that is
being investigated. In most studies, this is compared to another cause, named
the comparison. The outcome of interest is the effect. You will learn to use good
Causation 21